This Phase I SBIR grant application is in response to the Program Announcement for Development of Biomarkers for Mental Health Research. The goal of the proposed project is to develop a non-invasive electrophysiological device that will provide a biomarker for schizophrenia, which is a severe, heterogeneous mental disorder that leads to hallucinations and delusions, social withdrawal, and cognitive decline. While higher cognitive deficits have received a great deal of attention in schizophrenia research, a growing number of studies reveal deficits in early stages of visual processing. In particular, prominent deficits have been found in the magnocellular pathway, which conducts low-resolution spatial information rapidly to cortex and is involved in overall stimulus organization. Visual deficits are linked to higher-level functions, and visual function can be examined by obtaining electrophysiological recordings from surface electrodes placed on the scalp while specific stimuli are presented. These techniques have confirmed visual pathway dysfunction in schizophrenia. The ultimate goal of this project is to design a marketable medical instrument that can be used in clinical locations for the purposes of early detection of schizophrenia, identification of subgroups, indicating changes in severity, and monitoring of treatment regimens. This has clear implications for identification and treatment of a major psychiatric disorder. Currently, there is no electrophysiological device commercially available that contains prepackaged, automated stimulus paradigms and analysis techniques to assess visual function. The specific aims are to: 1) Develop user-friendly, automated hardware and software for precisely calibrated delivery of visual stimuli, based on specific sensory processing deficits in schizophrenia; 2) Build a device that is capable of recording electrophysiological responses from different brain regions in order to probe visual activity in each neural pathway and mechanism of interest and that decreases contamination from extraneous electrical signals, which is expected to increase sensitivity and specificity of the biomarker measures; 3) Develop user-friendly software for data analysis to enable automated rejection of corrupted signals and objective quantification of electrophysiological responses; 4) Apply the developed instrument in a pilot study of patients with schizophrenia and controls to identify a subset of critical test conditions which will be refined in a Phase II project to establish a composite VEP measure to serve as an efficacious biomarker. PUBLIC HEALTH RELEVANCE: Schizophrenia is a severe mental illness affecting 1% of the population. The goal of this Phase I SBIR application is to develop a user-friendly device that measures electrophysiological activity in the visual system, which has been shown to be profoundly impaired in schizophrenia. Of relevance to public health, this device is expected to provide a biomarker for this disorder and the ultimate goal is for it to be used in clinical settings for early detection of schizophrenia and monitoring of treatment regimens. [unreadable] [unreadable] [unreadable]